Pandemic Is Expediting Protocol Finalization in COVID-19 Studies

The worldwide rush demanded by the pandemic to develop and/or identify a potential treatment or vaccine has culminated in remarkable success in expediting COVID-19 trials, and the lessons learned are likely to be applied even after the pandemic is over.

The pandemic has led to a rapid speed-up in the time it takes to get from protocol finalization to first patient visit for COVID-19 studies. Investigators normally would finalize their trial protocols in a six-month process — perhaps three with great efficiency — and then proceed with site selection, contracting, budgeting and other tasks. Now, the majority of COVID trials are going from having a final protocol to first patient first visit in just four weeks, says Suzanne Caruso, WCG Clinical vice president of clinical solutions.

“We have a virus that basically didn’t exist five months ago, and now we have more than 950 active trials,” Caruso said at a WCG Clinical webinar last week. “Those are industry-sponsored trials, those are investigator-initiated trials. I think [the pandemic] forced a speed, and speed to getting trials ongoing is going to have a lasting impact on the clinical trial landscape beyond COVID.”

The numbers show that non-COVID, industry-sponsored trials have seen an enormous deceleration in participant enrollment and a massive increase in holds as a result of the pandemic. Prior to January, seven clinical trials were put on hold per month on average, according to WCG Clinical’s Knowledge Base. But as the pandemic developed, the number of paused trials rose sharply to 26 for March and utterly skyrocketed in April, when 129 studies were placed on official hold.

Industry has also seen an extreme slowdown in enrollment as a result of the outbreak; only 11 percent of clinical research sites across 29 different countries said that they were open to enrollment as of May 1, Caruso said. A little more than a month before, on March 24, 62 percent reported that they were open for enrollment — but just a week later, that number had plummeted to 26 percent and continued to drop afterward. Caruso noted, however, that she anticipates the number of trials open to enrollment will start to rise again in the near future.

Caruso referenced WCG Clinical data showing that with trial starts declining, the number of trials waiting to kick off have risen dramatically. Just in January, 629 new biopharma-sponsored studies were started, according to the data. That number declined to 546 in February, 492 in March, and descended sharply to 328 in April.

But the number of planned new trials skyrocketed from 223 in February to 463 in March and rose a tiny margin in April to 477.

Caruso pointed out that industry faces a collision of forces — a number of trials that are ongoing and soon to open to enrollment vs. a number of trials that are preparing to begin and will also open to enrollment.

“This is going to have tremendous impact as we come out of the COVID clinical trial landscape and turn to newer studies or ongoing studies,” she said. “The question really becomes, what do we do when we have this collision of new trials that our sponsors definitely want to get ongoing and enrolling well, as well as the restarts for studies that have been delayed as a result of that pause in enrollment?”

She cited a survey taken by WCG Clinical that probed how long sites think it will be before they open to enrollment again. The survey, which questioned more than 1,250 sites, found that more than a third (37 percent) of sites were uncertain, 26 percent anticipated four to eight weeks, and 19 percent believed it would take two to four weeks. Seven percent said one to two weeks, while just two percent said it would take more than two months.

But as of last week, WCG Clinical found that 51 percent of sites across 29 different countries reported they will be open to enrollment and new study starts within two to four weeks, she said.

Caruso said that right now, sites should be supporting study coordinators as they’re forced to cover more than they’re used to during the pandemic.

“There’s going to be tremendous impact in the amount of resources that the study coordinators have to cover for their new studies and COVID work,” she said. “There are going to be COVID trials for a number of months, if not years. Providing clinical research coordinators for a study to be able to do data entry, to be able to do scheduling of patients and keeping track, I think is the best way to support our site colleagues, and I think that’s something a lot of sponsors are looking into in addition to remote assessments and remote visits.”

Tom Wardle, CEO of CenExel Clinical Research, who also spoke during the webinar, offered advice on adapting trials to the pandemic. Successfully doing so requires taking a strong educational approach toward participants, he said, advising sponsors to develop and put in place standard operating procedures (SOP) for participants and employees, including testing for the virus.

“The response needs to be a lot of education, a lot of training, both to clinic personnel as well as training to potential study participants, and then even more importantly is demonstrating to study participants as they come in to potentially participate … that we’re showing them how seriously we are taking the precautions we need to take to try to minimize the risk of infection,” he said.

To minimize the risk of infection at a site, sponsors should develop a “formal pandemic SOP” that includes the use of personal protective equipment (PPE), procedures for entering the facility, testing procedures and other measures.

“At our facilities, you basically don’t get through the front door, and that means vendors, employees, participants in studies, without being screened in a kind of sequestered area,” he said. “You’re asking containment questions: have you been sick, where have you been, taking people’s temperature, asking about exposure to other individuals who may have had symptoms in the recent past.”

Additionally, sponsors should reduce the number of participants and staff in specific site areas, scheduling subjects throughout the day to ensure there is no high traffic of subjects at any point in the day. Facility access should be strictly limited, with staff receiving daily screenings upon arrival, and space should be designated to isolate symptomatic patients at a moment’s notice. And while it may seem obvious, Wardle reminded sponsors that infection control and facility cleaning is an important part of reducing infection risk.

Wardle reinforced the importance of remotely monitoring patients and enabling remote visits, following current Centers for Disease Control guidelines for screening employees and participants, and using COVID-19 polymerase chain reaction tests at screening, outpatient visits and inpatient unit entry. Patients and staff alike should be regularly reminded to continue the use of well-publicized guidelines for the coronavirus, such as the use of PPE, social distancing, hand sanitizer and other precautions.